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). Here, we exploit this dual functionality to track the potent nitrile-containing 5-lipoxygenase-activating protein (FLAP) antagonist BRP-685 in primary human macrophages using label-free spontaneous and stimulated Raman scattering. This approach enables direct intracellular localization at biologically relevant, low micromolar concentrations without chemical modification or external labels. Quantitative Raman imaging reveals that BRP-685 preferentially accumulates in lipid droplets, distinct from its membrane-bound target site at the nuclear envelope/endoplasmic reticulum. Multiplexed analysis with an alkyne-tagged lipid analog uncovers a unique distribution pattern, suggesting that lipid droplets act as intracellular reservoirs for highly lipophilic drugs.
Schultz et al. (Thu,) studied this question.